Tuberculosis

The Tuberculosis group is a dynamic, clinically-driven research group aiming to improve TB outcomes by combining high-quality laboratory science and clinical science.

Our current research objectives are improving TB diagnosis, treatment and prevention by carrying out clinical trials of new diagnostic tests, therapeutic approaches and vaccines. We also aim to understand the mechanisms by which both host and pathogen influence disease severity, treatment responses and outcomes using human macrophage models and omics technologies.

We focus on six research areas:

  • Diagnostics: developing and trialling novel tests based on pathogen detection and host response
  • Clinical trials: testing new drugs and repurposed old drugs
  • Prevention: trialling new vaccines in a community setting
  • Drug resistance: how it arises and how to diagnose it rapidly to improve outcomes
  • Pathogenesis: how bacterial variations affect disease severity and treatment outcomes
  • Host response: understanding immunological pathogenesis to develop host-directed therapies

 

Group Structure

Clinical Team

Clinical team members include study doctors, study nurses, study coordinators and data coordinators. The team’s responsibilities are working at hospitals and district TB units to recruit participants, making clinical assessments, taking samples, and follow-up until the end of the study.

Bacterial Lab

Bacterial lab team members include lab technicians, research assistants and PhD/post-doc scientists. 

The team works in our laboratories at OUCRU (clinical lab, BSL2 and BSL3 labs). They are responsible for running all the microbiological lab tests (diagnosis tests, drug-susceptible and tolerance testing) required by all studies and managing many types of samples. Some of these tests are routine TB tests; some are novel tests which are still in the development and research stage.

Cell-Immunological Lab

Similar to the Bacterial Lab team, the Cell-Immunological lab team members work in our labs at OUCRU. The team works mainly on cells, molecular lab experiments and analysis, which include host-pathogen interaction, cytokines, whole genome sequencing (WGS), next-generation sequencing (NGS) and omics.

Data Team

Data team members include research assistants and PhD/post-doc biostatisticians who are in charge of analysing data collected by the clinical team and lab teams. Their works focus on omics, WGS and NGS.

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Tuberculosis Meningitis (TBM) in Children

The Paediatrics TBM team structure is similar to the clinical team. The team is working on clinical trials and observational studies in diagnosing and treating TBM in children.

Epi-Microbiology

The epi-Microbiology team structure is similar to the clinical team. The team is conducting many observational-epidemiological studies and genetic data analysis focusing on drug resistance, epi-microbiology, and epi-genomics of TB and TB vaccine.

Key Achievements

Defining TB drug resistance and transmission

Associations between cell size and structure and drug resistance have been shown (Vijay et al Front Microbiol 2017 & 2018), whilst the spread of the Beijing lineage and positive selection of the EsxW Beijing variant in Vietnam have also been demonstrated (Holt et al Nature 2018); Sources of multi-drug resistance (Vijay et al CID 2020); Risk factors for poor treatment outcomes of multidrug-resistant TB (Van et al BMC 2020). 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: A genotypic analysis (Walker et al Lancet Microbe 2022).

Improving diagnostic methods in TBM

We defined the use of GeneXpert MTB/RIF in the diagnosis of TBM (Nhu et al JCM 2014) and pediatric TB (Giang et al BMC 2015). The largest prognostic study to date of mortality in TBM with 1699 cases (Thao et al CID 2018Thao et al CID 2020) identified predictors for increased mortality. Xpert MTB/RIF Ultra for the diagnosis of TBM (Donovan et al CID 2020). Cepheid 3-gene host response fingerstick blood test for PTB diagnosis (Sutherland et al CID 2022).

Defining TB susceptibility and pathogenesis

Human Leukotriene A4 Hydrolase (LTA4H) genotype was found to determine TBM susceptibility and predict the effectiveness of adjunctive dexamethasone (Tobin et al Cell 2010 and 2012Thuong et al JID 2017). Two large multi-centre clinical trials to personalised TBM treatment are underway (Donovan et al Wellcome Open Res 2018). Effect of bacterial burden on inflammatory response and outcome (Thuong et al JID 2019Hai et al Tuberculosis 2021).

Improving treatment outcomes from TBM

Dexamethasone (now endorsed by WHO for TBM treatment) saves more lives (Thwaites et al NEJM 2004); timing of ARVs does not influence survival (Torok et al CID 2011); intensified TB therapy improves survival in INH-R TBM (Heemskerk et al NEJM 2016Heemskerk et al CID 2017); phase 2 trial of adjunctive aspirin for TBM (Mai et al Elife 2018).

Key Publications

Thuong NTT, Heemskerk D, Tram TTB, et al. Leukotriene A4 Hydrolase Genotype and HIV Infection Influence Intracerebral Inflammation and Survival From Tuberculous Meningitis. J Infect Dis. 2017;215(7):1020-1028. https://pubmed.ncbi.nlm.nih.gov/28419368/

Mai NT, Dobbs N, Phu NH, et al. A randomised double blind placebo controlled phase 2 trial of adjunctive aspirin for tuberculous meningitis in HIV-uninfected adults. Elife. 2018;7:e33478. https://pubmed.ncbi.nlm.nih.gov/29482717/

Van LH, Phu PT, Vinh DN, et al. Risk factors for poor treatment outcomes of 2266 multidrug-resistant tuberculosis cases in Ho Chi Minh City: a retrospective study. BMC Infect Dis. 2020;20(1):164. https://pubmed.ncbi.nlm.nih.gov/32087682/

Tram TTB, Ha VTN, Thu DDA, et al. Variations in Antimicrobial Activities of Human Monocyte-Derived Macrophage and Their Associations With Tuberculosis Clinical Manifestations. Front Cell Infect Microbiol. 2020;10:586101. https://pubmed.ncbi.nlm.nih.gov/33194825/

Sutherland JS, van der Spuy G, Gindeh A, et al. Diagnostic Accuracy of the Cepheid 3-gene Host Response Fingerstick Blood Test in a Prospective, Multi-site Study: Interim Results. Clin Infect Dis. 2022;74(12):2136-2141. https://pubmed.ncbi.nlm.nih.gov/34550342/

Walker TM, Miotto P, Köser CU, et al. The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: A genotypic analysis. Lancet Microbe. 2022;3(4):e265-e273. https://pubmed.ncbi.nlm.nih.gov/35373160/

Publications

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Sydney Stanley, Caitlin N Spaulding, Qingyun Liu, Michael R Chase, Dang Thi Minh Ha, Phan Vuong Khac Thai, Nguyen Huu Lan, Do Dang Anh Thu, Nguyen Le Quang, Jessica Brown, Nathan D Hicks, Xin Wang, Maximillian Marin, Nicole C Howard, Andrew J Vickers, Wiktor M Karpinski, Michael C Chao, Maha R Farhat, Maxine Caws, Sarah J Dunstan, Nguyen Thuy Thuong Thuong, Sarah M Fortune
Lancet Microbe
May 6, 2024
DOI: 10.1016/S2666-5247(24)00022-3
Hung Van Nguyen, Hoa Binh Nguyen, Doan Thu Ha, Dinh Thi Huong, Vu Ngoc Trung Khieu Thi Thuy Ngoc, Tran Huyen Trang, Ha Vu Thi Ngoc, Tram Trinh Thi Bich, Trieu Le Pham Tien, Hanh Nguyen Hong, Phu Phan Trieu, Luong Kim Lan, Kim Lan, Ngo Ngoc Hue, Nguyen Thi Le Huong, Tran Le Thi Ngoc Thao, Nguyen Le Quang, Thu Do Dang Anh, Nguy%u1EC5n H%u1EEFu L%E2n, Truong Van Vinh, Dang Thi Minh Ha, Phan Thuong Dat, Nguyen Phuc Hai, Derrick W Crook, Nguyen Thuy Thuong Thuong, Nhung Viet Nguyen, Guy E Thwaites, Timothy M Walker
J Clin Tuberc Other Mycobact Dis.
March 24, 2024
DOI: 10.1016/j.jctube.2024.100431
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Hospital For Tropical Diseases

BVP

National Lung Hospital

NTP

Nguyen Tri Phuong Hospital

PNTH

Pham Ngoc Thach Hospital

BYT

Vietnam National TB Program

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Associate Professor Jayne Sutherland

Associate Professor Sarah Dunstan

Associate Professor Sarah Dunstan

Thuy Le

Associate Professor Thuỷ Lê

Professor Derrick Crook

Professor Derrick Crook

Professor Diana Gibb

Professor Diana Gibb

Professor Gerhard Walzl

Professor Gerhard Walzl

Professor Lallita Ramakrishnan

Professor Lallita Ramakrishnan

Professor Reinout van Crevel

Professor Reinout van Crevel

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Professor Thomas Hawn

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